- A simple and convenient synthesis of pyrazinones
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Pyrazinones were synthesized by reacting mesoionic azlactone [2-aryl-4-methyl-Δ2-oxaxolin-5-one] and 1,4-diazabutadienes in good yields at room temperature. Copyright Taylor & Francis Group, LLC.
- Sharma, Saikat Das,Gogoi, Pranjal,Konwar, Dilip
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- Origin of Enantioselectivity in Chiral Phosphoric-Acid-Catalyzed Azlactone Dynamic Kinetic Resolution
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Theoretical calculations, associated with control experiments, were carried out to gain insights into the mechanism and origin of enantioselectivity in the phosphoric-acid-catalyzed dynamic kinetic resolution of azlactones. The results revealed a Münchnon
- Amarante, Giovanni W.,Batista, Gabriel M. F.,De Castro, Pedro P.,Dos Santos, Helio F.
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p. 13169 - 13174
(2021/09/18)
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- Palladium-Catalyzed Allenamide Carbopalladation/Allylation with Active Methine Compounds
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A palladium-catalyzed allenamide carbopalladation/allylation with active methine compounds has been developed. Various indoles and isoquinolinones bearing a quaternary carbon center were achieved with good efficiency, a broad substrate scope and good functional group tolerance. This reaction underwent cascade oxidative addition, carbopalladation, and allylic alkylation, and two new C-C bonds were formed in one pot.
- Zhu, Xiaoyi,Li, Ruibo,Yao, Hequan,Lin, Aijun
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supporting information
p. 4630 - 4634
(2021/06/28)
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- Organocatalytic asymmetric [4+2] cyclization of 2-benzothiazolimines with azlactones: Access to chiral benzothiazolopyrimidine derivatives
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An organocatalytic asymmetric domino Mannich/cyclization reaction between 2-benzothiazolimines with azlactones has been successfully developed. With the bifunctional squaramide catalyst, this formal [4+2] cyclization occurs with good to high yields and excellent stereoselectivities (up to 99% ee, >20?:?1 dr), providing an efficient and mild access to chiral benzothiazolopyrimidines bearing adjacent tertiary and quaternary stereogenic centers.
- Ni, Qijian,Wang, Xuyang,Xu, Fangfang,Chen, Xiaoyun,Song, Xiaoxiao
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supporting information
p. 3155 - 3158
(2020/03/23)
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- A step-economic and one-pot access to chiral Cα-tetrasubstituted α-amino acid derivatives: Via a bicyclic imidazole-catalyzed direct enantioselective C -acylation
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Cα-Tetrasubstituted α-amino acids are ubiquitous and unique structural units in bioactive natural products and pharmaceutical compounds. The asymmetric synthesis of these molecules has attracted a lot of attention, but a more efficient method is still greatly desired. Here we describe the first sequential four-step acylation reaction for the efficient synthesis of chiral Cα-tetrasubstituted α-amino acid derivatives from simple N-acylated amino acids via an auto-tandem catalysis using a single nucleophilic catalyst. The synthetic efficiency is improved via a direct enantioselective C-acylation; the methodology affords the corresponding Cα-tetrasubstituted α-amino acid derivatives with excellent enantioselectivities (up to 99% ee). This step-economic, one-pot, and auto-tandem strategy provides facile access to important chiral building blocks, such as peptides, serines, and oxazolines, which are often used in medicinal and synthetic chemistry.
- Wang, Mo,Zhang, Lu,Zhang, Wanbin,Zhang, Zhenfeng,Zhou, Muxing
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p. 4801 - 4807
(2020/06/18)
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- Transformation of Racemic Azlactones into Enantioenriched Dihydropyrroles and Lactones Enabled by Hydrogen-Bond Organocatalysis
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Azlactones, a potent building block for the synthesis of complex molecules, have been explored in an organocatalytic Mannich reaction with protected imines. In this study, azlactones containing a propargyl substituent were employed for the first time in organocatalysis so far. The catalytically active species responsible for high enantioselectivity with substrate containing such a small linear substituent is assembled in situ from a bifunctional thiourea, prone to dimerization, and an organic acid, as evidenced by DOSY NMR. The resulting α,β-diamino acid derivatives were subjected to further derivatization: as an example, gold-catalyzed intramolecular hydroamination of alkynes gave chiral spirocyclic dihydropyrrole. Alternatively, related squaramide catalyst enabled a Mannich reaction of azlactones with N-aryl or alkyl glyoxylate imines. Reduction of these adducts gave access to 2,3-diaminobutyrolactones or 2,3-diamino-1,4-diol with a tertiary and a quaternary stereocenter.
- ?abka, Matej,Kocian, Adrián,Bilka, Stanislav,Andrej?ák, Samuel,?ebesta, Radovan
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p. 6077 - 6087
(2019/09/12)
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- Synthesis and Anti-HIV Profile of a Novel Tetrahydroindazolylbenzamide Derivative Obtained by Oxazolone Chemistry
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A new tetrahydroindazolylbenzamide derivative has been synthesized, characterized, and evaluated as HIV-inhibitor. The biological data revealed the ability to inhibit HIV proliferation with low cytotoxicity allowing for significant selectivity (EC50
- Scala, Angela,Piperno, Anna,Micale, Nicola,Christ, Frauke,Debyser, Zeger
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p. 398 - 401
(2019/04/25)
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- Asymmetric construction of dihydrobenzofuran-2,5-dione derivatives via desymmetrization of p-quinols with azlactones
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The desymmetrization of p-quinols through a chiral bisguanidinium hemisalt catalyzed enantioselective Michael addition/lactonization cascade reaction with azlactones was reported. 3-Amino-benzofuran-2,5-diones containing a chiral amino acid residue were achieved with up to 99% ee and >19?:?1 dr. An exploration of the structure of the catalyst bisguanidinium was undertaken, revealing a bifunctional catalytic model.
- Xie, Lihua,Dong, Shunxi,Zhang, Qian,Feng, Xiaoming,Liu, Xiaohua
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supporting information
p. 87 - 90
(2019/01/03)
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- Palladium-catalyzed asymmetric decarboxylative allylation of azlactone enol carbonates: Fast access to enantioenriched α-allyl quaternary amino acids
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We report a fast protocol for the synthesis of enantioenriched quaternary 4-allyl oxazol-5-ones. The key step is a Pd-catalyzed enantioselective Tsuji allylation of azlactone allyl enol carbonates, which can be easily prepared starting from racemic α-amino acids. The use of (R,R)-DACH-phenyl Trost chiral ligand allowed the attainment of the allylated derivatives in very good yields (83–98 %) and with ee up to 85 %. Scaling up the allylation protocol to gram quantities did not affect the yields end ee values. The produced 4-allyl azlactones can be converted into the corresponding quaternary amino acids or submitted to further synthetic elaborations exploiting the allyl moiety as a handle for the attachment of alkyl and aryl groups. After hydrolysis of the azlactone ring, the zwitterionic amino acids can be attained in enantiopure or nearly optically pure form through only one recrystallization step.
- Serra, Massimo,Bernardi, Eric,Marrubini, Giorgio,De Lorenzi, Ersilia,Colombo, Lino
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p. 732 - 741
(2019/01/09)
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- Metal-Free Insertion Reactions of Diazo Carbonyls to Azlactones
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Insertion reactions of diazo carbonyls to azlactones in basic conditions have been performed. The developed method allows the preparation of a wide range of oxazole derivatives in yields ranging from 74 to 98%. Different substituents on both azlactone rings and diazo carbonyls do not compromise the methodology, even those containing stereogenic centers. Isotopic labeling experiments revealed the mechanism may proceed through a rare diazo carbonyl activation by an ammonium salt derivative.
- De Mello, Amanda C.,Momo, Patrícia B.,Burtoloso, Antonio C. B.,Amarante, Giovanni W.
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p. 11399 - 11406
(2018/09/12)
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- Group-Assisted Purification Chemistry for Asymmetric Mannich-type Reaction of Chiral N-Phosphonyl Imines with Azlactones Leading to Syntheses of α-Quaternary α,β-Diamino Acid Derivatives ?
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An asymmetric Mannich-type reaction between chiral N-phosphonyl imines and azlactones [oxazol-5(4H)-ones] has been established under convenient conditions at room temperature. The reaction was performed without using any bases, additives, or catalysts to achieve up to excellent chemical yields and diastereoselectivity for 32 examples. The α-quaternary syn-α,β-diamino acid products were purified simply by washing the crude mixtures with cosolvents, following the group-assisted purification chemistry/technology, without involving traditional chromatography or recrystallization methods. The auxiliary can be readily removed and recycled for reuse. The absolute configuration was unambiguously assigned by X-ray structural analysis.
- Zhang, Haowei,Yang, Zhen,Zhao, Brian Nlong,Li, Guigen
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p. 644 - 655
(2018/01/27)
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- STRUCTURE AND SYNTHESIS OF HIGHLY FLUORINATED AMINO ACID DERIVATIVES
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Methods of synthesizing polyfluorinated amino acid derivatives are disclosed, along with polyfluorinated amino acid derivatives produced from said methods, as well as compositions containing same. The synthesis methods utilize an oxazolone and a perfluoroarene to produce the polyfluorinated amino acid derivatives.
- -
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Paragraph 0170; 0171; 0172; 0173
(2018/09/19)
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- Polyfluoroarylation of oxazolones: Access to non-natural fluorinated amino acids
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Herein, conditions are provided for the formation and use of the oxazolone enolate for the nucleophilic substitution of highly fluorinated (hetero)arenes, which after unmasking yield highly fluorinated non-natural amino acids and derivatives. In addition, the properties and chemical behavior of this new class of amino acids are explored. The utility is demonstrated in the one pot synthesis of medicinally relevant 2-aminohydantoins.
- Teegardin, Kip A.,Weaver, Jimmie D.
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supporting information
p. 4771 - 4774
(2017/07/06)
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- One-Pot Vinylation of Azlactones: Fast Access to Enantioenriched α-Vinyl Quaternary Amino Acids
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We report a fast one-pot protocol for the direct vinylation of azlactones [oxazol-5-(4H)-ones] by using as a key step an aldol addition with 2-(phenylselenenyl)acetaldehyde followed by dehydroxyselenation. The acid hydrolysis of the oxazolone ring gave the desired fully deprotected α-vinyl quaternary α-amino acids in almost quantitative yields. An enantioselective variant of the method was also developed by using catalytic chiral bases. The use of Sharpless ligand (DHQD)2PHAL produced the final quaternary amino acids in good overall yields (62–78 %) and with ee values up to 86 %. Scaling up the optimized protocol to gram quantities did not affect the yields and ee values. We also demonstrated that the vinyl moiety installed onto the oxazolone ring can be exploited as a handle for the attachment of aryl groups through a Heck coupling reaction.
- Serra, Massimo,Bernardi, Eric,Marrubini, Giorgio,Colombo, Lino
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p. 2964 - 2970
(2017/06/06)
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- SELENOCYSTINE DERIVATIVES, ALPHA-METHYLSELENOCYSTEINE, ALPHA-METHYLSELENOCYSTEINE DERIVATIVES, AND METHODS OF MAKING AND USING SAME
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Provided are selenocysteine derivatives (e.g., deuterium and tritium analogs), α-methylselenocysteine, and α-methylselenocysteine derivatives. These compounds can be incorporated in more complex chemical structures (e.g., polymers, proteins, peptides, and
- -
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Paragraph 0083
(2016/08/29)
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- Regiodivergent Enantioselective γ-Additions of Oxazolones to 2,3-Butadienoates Catalyzed by Phosphines: Synthesis of α,α-Disubstituted α-Amino Acids and N,O-Acetal Derivatives
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Phosphine-catalyzed regiodivergent enantioselective C-2- and C-4-selective γ-additions of oxazolones to 2,3-butadienoates have been developed. The C-4-selective γ-addition of oxazolones occurred in a highly enantioselective manner when 2-aryl-4-alkyloxazol-5-(4H)-ones were employed as pronucleophiles. With the employment of 2-alkyl-4-aryloxazol-5-(4H)-ones as the donor, C-2-selective γ-addition of oxazolones took place in a highly enantioselective manner. The C-4-selective adducts provided rapid access to optically enriched α,α-disubstituted α-amino acid derivatives, and the C-2-selective products led to facile synthesis of chiral N,O-acetals and γ-lactols. Theoretical studies via DFT calculations suggested that the origin of the observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic oxazolide and the electrophilic phosphonium intermediate.
- Wang, Tianli,Yu, Zhaoyuan,Hoon, Ding Long,Phee, Claire Yan,Lan, Yu,Lu, Yixin
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supporting information
p. 265 - 271
(2016/01/25)
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- Enantioselective synthesis of dihydrocoumarin derivatives by chiral scandium(iii)-complex catalyzed inverse-electron-demand hetero-Diels-Alder reaction
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An asymmetric inverse-electron-demand hetero-Diels-Alder reaction between o-quinone methides and azlactones to generate potentially pharmacological active dihydrocoumarins has been achieved efficiently by using a chiral N,N′-dioxide-Sc(iii) complex as the catalyst. The desired products were obtained in high yields with excellent enantioselectivities and diastereoselectivities (up to 94% yield, 96% ee and >19:1 dr) under mild reaction conditions. A concerted reaction pathway was confirmed by Operando IR and control experiments.
- Hu, Haipeng,Liu, Yangbin,Guo, Jing,Lin, Lili,Xu, Yali,Liu, Xiaohua,Feng, Xiaoming
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supporting information
p. 3835 - 3837
(2015/03/31)
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- Alkynyliodonium salt mediated alkynylation of azlactones: Fast access to Cα-tetrasubstituted α-amino acid derivatives
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An efficient electrophilic alkynylation of azlactones (oxazol-5(4H)-ones) is developed using alkynyl(phenyl)iodonium salts as the electrophilic alkyne source. After remarkably short reaction times, the desired alkyne functionalized azlactones are obtained in 60-97% yield and can be transformed easily into a variety of quaternary α-amino acid derivatives.
- Finkbeiner, Peter,Weckenmann, Nicole M.,Nachtsheim, Boris J.
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supporting information
p. 1326 - 1329
(2014/04/03)
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- Catalyst-free synthesis of N -(1,7-dioxotetrahydropyrazolo[1,2-a]pyrazol-2- yl)benzamide derivatives by 1,3-dipolar cycloaddition and rearrangement
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N-(1,7-Dioxotetrahydropyrazolo[1,2-a]pyrazol-2-yl)-benzamide derivatives, a novel class of compounds, were synthesized by 1,3-dipolar cycloaddition of azomethine imines with azlactones and subsequent rearrangement. The reaction can be completed rapidly under mild conditions without a catalyst. Georg Thieme Verlag Stuttgart New York.
- Liu, Wenjing,Xu, Yu,Sun, Xingxia,Lu, Dapeng,Guo, Lijuan
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supporting information
p. 1093 - 1096
(2014/05/20)
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- Bronsted acid accelerated Pd-catalyzed direct asymmetric allylic alkylation of azlactones with simple allylic alcohols: A practical access to quaternary allylic amino acid derivatives
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A Bronsted acid accelerated Pd-catalyzed asymmetric allylic alkylation of azlactones with simple allylic alcohols under mild reaction conditions has been realized, which provides a direct and readily scalable approach for the synthesis of all-carbon quaternary allylic amino acid derivatives in excellent yields and good enantioselectivities. (Chemical Equation Presented).
- Zhou, Hui,Yang, Huameng,Liu, Muwen,Xia, Chungu,Jiang, Gaoxi
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supporting information
p. 5350 - 5353
(2015/01/09)
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- Organocatalyzed asymmetric 1,4-addition of azlactones to α,β-unsaturated trichloromethyl ketones: Synthesis of α,α-disubstituted α-amino acid derivatives
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The first asymmetric 1,4-addition of azlactones to α,β-unsaturated trichloromethyl ketones catalyzed by cinchona alkaloid derived bifunctional thiourea catalysts was developed. A series of α,α-disubstituted α-amino acid derivatives bearing a quaternary stereocenter at the α-position were obtained in high yields with excellent diastereo- and enantioselectivities (up to -20:1 dr and 99% ee). In addition, the trichloromethyl moiety in these adducts was identified as a good leaving group.
- Zhang, Jinlong,Liu, Xihong,Wu, Chongyang,Zhang, Panpan,Chen, Jianbo,Wang, Rui
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supporting information
p. 7104 - 7108
(2015/01/16)
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- BEMP-promoted C(4)-alkylation of 4-alkyloxazol-5(4 H)-ones: A rapid and efficient route to α,α-dialkyl-α-amino acids
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Rapid and efficient C(4)-alkylation of 4-alkyloxazol-5(4H)-ones has been achieved by the utilization of BEMP as base. 4,4-Dialkyloxazol-5(4H)-ones, which can easily be hydrolyzed into free α,α-dialkyl-α-amino acids, were obtained in high yields (up to 99%
- Lee, Yeon-Ju,Seo, Jeyoung,Kim, Dong-Guk,Park, Hyeung-Geun,Jeong, Byeong-Seon
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p. 701 - 704
(2013/05/09)
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- Synthesis of di- and tri-substituted imidazole-4-carboxylates via PBu3-mediated [3+2] cycloaddition
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Some new di- and trisubstituted imidazole-4-carboxylates were prepared from amidoacetic acids 3 in the present report. The key step to establish such imidazole- 4-carboxylates stemmed from the PBu3-mediated [3+2] cycloaddition between in situ-generated Δ2-oxazolinone 4 and ethyl cyanoformate6. Our results indicated that trisubstituted imidazoles 7-20 were afforded in better yields than those of disubstituted imidazoles 21-27. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Hsu, Mei-Yuan,Dietrich, Justin,Hulme, Christopher,Shaw, Arthur Y.
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p. 1538 - 1542
(2013/05/21)
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- 5(4H)-oxazolones as intermediates in the carbodiimide- and cyanamide-promoted peptide activations in aqueous solution
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The early days: Although considered a species to be avoided in peptide chemistry, the intermediacy of 5(4H)-oxazolones is demonstrated to be essential for the formation of peptides through cyanamide and carbodiimide activation in aqueous solution (see sch
- Danger, Grégoire,Michaut, Arthur,Bucchi, Manon,Boiteau, Laurent,Canal, Justine,Plasson, Rapha?l,Pascal, Robert
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supporting information
p. 611 - 614
(2013/02/23)
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- Bispalladacycle-catalyzed Michael addition of in situ formed azlactones to enones
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The development and further evolution of the first catalytic asymmetric conjugate additions of azlactones as activated amino acid derivatives to enones is described. Whereas the first-generation approach started from isolated azlactones, in the second-generation approach the azlactones could be generated in situ starting from racemic N-benzoylated amino acids. The third evolution stage could make use of racemic unprotected α-amino acids to directly form highly enantioenriched and diastereomerically pure masked quaternary amino acid products bearing an additional tertiary stereocenter. The step-economic transformations were accomplished by cooperative activation by using a robust planar chiral bis-Pd catalyst, a Br?nsted acid (HOAc or BzOH; Ac=acetyl, Bz=benzoyl), and a Br?nsted base (NaOAc). In particular the second- and third-generation approaches provide a rapid and divergent access to biologically interesting unnatural quaternary amino acid derivatives from inexpensive bulk chemicals. In that way highly enantioenriched acyclic α-amino acids, α-alkyl proline, and α-alkyl pyroglutamic acid derivatives could be prepared in diastereomerically pure form. In addition, a unique way is presented to prepare diastereomerically pure bicyclic dipeptides in just two steps from unprotected tertiary α-amino acids. Flourishing step economy: The evolution of the catalytic asymmetric addition of azlactones to enones is described. The first-generation approach started from isolated azlactones. In the second-generation approach azlactones could be generated in situ from racemic N-benzoylated amino acids. The third evolution stage could directly use racemic unprotected α-amino acids to form a large number of highly enantioenriched quaternary amino acids derivatives (see figure). Copyright
- Weber, Manuel,Jautze, Sascha,Frey, Wolfgang,Peters, René
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supporting information
p. 14792 - 14804
(2013/01/15)
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- One-pot synthesis of 2,4,5-trisubstituted oxazoles from N-acyl amino acids by a combination of cyclodehydration with N,N′-diisopropylcarbodiimide and Wittig olefination
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By a combination of cyclodehydration of N-acyl amino acids with N,N′-diisopropylcarbodiimide (DIC) and non-classical Wittig olefination of the resultant 5(4H)-oxazolones with Ph3PCHCN and Ph 3PCHCOOEt, 5-oxazoleacetonitriles and 5-oxazoleacetates were synthesized in one-pot in 41-85% and 57-70% yields, respectively.
- Huang, Wenhua,Dong, Guangping,Mijiti, Zumureti
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experimental part
p. 977 - 981
(2012/02/13)
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- Self-association free bifunctional thiourea organocatalysts: Synthesis of chiral α-amino acids via dynamic kinetic resolution of racemic azlactones
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Concentration-independent high enantioselectivity in the dynamic kinetic resolution (DKR) of racemic azlactones affording chiral α-aminoesters has been achieved using self-association free thiourea-based dimeric cinchona alkaloid organocatalysts. Detailed
- Oh, Joong-Suk,Lee, Ji-Woong,Ryu, Tae Hee,Lee, Jae Heon,Song, Choong Eui
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experimental part
p. 1052 - 1055
(2012/04/10)
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- Enantioselective quaternization of 4-substituted oxazol-5-(4H)-ones using recoverable Cinchona-derived dimeric ammonium salts as phase-transfer organocatalysts
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Dimeric anthracenyldimethyl-derived Cinchona ammonium salts are used as chiral organocatalysts (5 mol %) for the enantioselective 4-alkylation of 4-substituted azlactones. The corresponding adducts bearing a new quaternary center were obtained with up to
- Tari, Silvia,Avila, Angel,Chinchilla, Rafael,Najera, Carmen
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experimental part
p. 176 - 180
(2012/05/20)
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- One-pot preparation of oxazol-5(4H)-ones from amino acids in aqueous solvents
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A method for one-pot synthesis of oxazol-5(4H)-ones has been developed using 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which is available for the activation of carboxylic acids in an aqueous solvent. The oxazolones were prepared by the TV-acylation of amino acids with carboxylic acids and the subsequent cyclodehydration of the resulting N-acylamino acids by the addition of N,N-diethylaniline. Since both these reactions proceed effectively with the same coupling reagent, DMT-MM, in aqueous solvents, the procedure is simplified and becomes easy to perform. In addition, 5-(triazinyloxy)oxazole derivatives have been synthesized by controlling the basicity of the reaction system.
- Fujita, Hikaru,Kunishima, Munetaka
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p. 907 - 912
(2012/08/08)
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- Asymmetric synthesis of 3, 4-diaminochroman-2-ones promoted by guanidine and bisguanidium salt
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A highly enantioselective synthesis of 3,4-diaminochroman-2-ones has been realized via the domino reaction of o-hydroxy aromatic aldimines and azlactones. Notably, a cis-product was obtained as the major product by the use of guanidine 2a whereas a trans-product was the major product with bisguanidium salt 3·HBArF 4. In two cases, various substituted 3,4-dihydrocoumarins were obtained with high yields (up to 99%) as well as excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to >99:1 cis:trans and 98:2 trans:cis, respectively) under mild reaction conditions.
- Dong, Shunxi,Liu, Xiaohua,Zhang, Yulong,Lin, Lili,Feng, Xiaoming
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supporting information; experimental part
p. 5060 - 5063
(2011/12/05)
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- Bispalladacycle-catalyzed bronsted acid/base-promoted asymmetric tandem azlactone formation-michael addition
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Cooperative activation by a soft bimetallic catalyst, a hard Bronsted acid, and a hard Bronsted base has allowed the formation of highly enantioenriched, diastereomerically pure masked α-amino acids with adjacent quaternary and tertiary stereocenters in a single reaction starting from racemic N-benzoylated amino acids. The products can, for example, be used to prepare bicyclic dipeptides.
- Weber, Manuel,Jautze, Sascha,Frey, Wolfgang,Peters, Rene
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supporting information; experimental part
p. 12222 - 12225
(2010/11/03)
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- Synthesis of 1,2,4-Triazolines and triazoles utilizing oxazolones
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We describe herein a convenient method for the synthesis of 1,2,4-triazolines using oxazolones and azodicarboxylates. Subsequent treatment of these 1,2,4-triazolines with NaOH provides efficient access to the corresponding triazoles.
- Saleem, Rahman Shah Zaib,Tepe, Jetze J.
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supporting information; experimental part
p. 4330 - 4332
(2010/09/03)
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- Dynamic kinetic resolution of N-benzoyl-DL-amino acids via peptide bond forming reactions
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Dynamic kinetic resolution (DKR) was demonstrated in the carbodiimide-mediated couplings of N-benzoyl-DL-amino acids with L-amino acid esters: the yields of the D-L-peptides significantly exceeded 50% in some cases. N-benzoyl-DL-t-leucine afforded the D-L-peptide almost exclusively (up to 96% yield) in the reaction with methyl L-prolinate, which is the most efficient DKR obtained in the field of amino acids and derivatives.
- Miyazawa, Toshifumi,Hamada, Takashi
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body text
p. 419 - 422
(2011/12/04)
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- Structural-activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-κB mediated IL-6 production
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We herein describe the synthesis and anti-inflammatory properties of a small library of imidazoline-based NF-κB inhibitors. The structure-activity relationship of various substituents on an imidazoline core structure was evaluated for the ability to inhibit NF-κB mediated IL-6 production. Optimization of the scaffolds was pursued by correlating luciferase-based NF-κB reporter assays with inhibition of IL-6 production in IL-1β stimulated human blood. Several derivatives were found to inhibit NF-κB mediated IL-6 production in the nanomolar range in IL-1β stimulated human blood.
- Kahlon, Daljinder K.,Lansdell, Theresa A.,Fisk, Jason S.,Tepe, Jetze J.
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body text
p. 3093 - 3103
(2009/10/02)
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- Eleven amino acid glucagon-like peptide-1 receptor agonists with antidiabetic activity
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Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid peptide hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report the discovery of a novel class of 11 amino acidGLP-1 receptor agonists. These peptides consist of a structurally optimized 9- mer, which is closely related to the N-terminal 9 amino acids ofGLP-1, linked to a substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar in vitro potency to the native 30-mer. Peptides 21 and 22 acutely reduced plasma glucose excursions and increased plasma insulin concentrations in a mouse model of diabetes. These peptides also showed sustained exposures over several hours in mouse and dog models. The described 11-mer GLP-1 receptor agonists represent a new tool in further understanding GLP-1 receptor pharmacology that may lead to novel antidiabetic agents.
- Mapelli, Claudio,Natarajan, Sesha I.,Meyer, Jean-Philippe,Bastos, Margarita M.,Bernatowicz, Michael S.,Lee, Ving G.,Pluscec, Jelka,Riexinger, Douglas J.,Sieber-McMaster, Ellen S.,Constantine, Keith L.,Smith-Monroy, Constance A.,Golla, Rajasree,Ma, Zhengping,Longhi, Daniel A.,Shi, Dan,Xin, Li,Taylor, Joseph R.,Koplowitz, Barry,Chi, Cecilia L.,Khanna, Ashish,Robinson, Gordon W.,Seethala, Ramakrishna,Antal-Zimanyi, Ildiko A.,Stoffel, Robert H.,Han, Songping,Whaley, Jean M.,Huang, Christine S.,Krupinski, John,Ewing, William R.
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experimental part
p. 7788 - 7799
(2010/06/16)
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- A new method proposed for the determination of absolute configurations of α-amino acids
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Enantiopure α-amino acids were converted to 4-substituted 2-aryl- and 2-alkyl-5(4H)-oxazolones under partial racemization. These nonracemic mixtures were dissolved in CDCl3, an equimolar amount of the chiral dirhodium complex Rh2(II)[(R)-(+)-MTPA]4 (MTPA-H = Mosher's acid) was added, and the 1H NMR spectra of the resulting samples were recorded [dirhodium method). The relative intensities of 1H signals dispersed by the formation of diastereomeric adducts allow to determine the absolute configuration (AC) of the starting a-amino acids. Binding atoms in the adducts were identified by comparing the 1H and 13C chemical shifts of the oxazolones in the absence and presence of Rh2(II)[(R)-(+)- MTPA]4. Thereby, information about the scope and limits of this method can be extracted. A protocol how to use this method is presented. Copyright
- Gomez, Edison Diaz,Duddeck, Helmut
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experimental part
p. 222 - 227
(2010/02/28)
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- A magnetic-nanoparticle-supported 4-N,N-dialkylaminopyridine catalyst: Excellent reactivity combined with facile catalyst recovery and recyclability
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(Figure Presented) Quick recovery: The first magnetic-nanoparticle- supported organocatalyst is prepared. The heterogeneous catalyst promotes a range of nucleophilic reactions and can be recovered by exposure to an external magnet (see picture). Furthermore, it can be recycled over 30 times without loss of activity.
- O Dalaigh, Ciaran,Corr, Serena A.,Gun'ko, Yurii,Connon, Stephen J.
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p. 4329 - 4332
(2008/03/11)
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- Au(I)-catalyzed enantioselective 1,3-dipolar cycloadditions of muenchnones with electron-deficient alkenes
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The first catalytic enantioselective 1,3-dipolar cycloaddition of muenchnone dipoles with electron-deficent alkenes is described. The reaction is catalyzed by chiral bis(phosphine)gold(I) benzoate complexes and provides Δ1-pyrrolines with excellent regio-, diastereo-, and enantioselectivity. The reaction is proposed to proceed througha 1,3-dipole generated by deprotonation of a gold(I)-activated azlactone. Copyright
- Melhado, Asa D.,Luparia, Marco,Toste, F. Dean
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p. 12638 - 12639
(2008/03/14)
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- Diastereochemical diversity of imidazoline scaffolds via substrate controlled TMSCI mediated cycloaddition of azlactones
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(Chemical Equation Presented) We report herein a trimethylsilyl chloride mediated substrate controlled 1,3-dipolar cycloaddition for the diastereoselective synthesis of either syn- or anti-imidazolines. This method provides scaffolds with four points of diversity and control over two stereocenters.
- Sharma, Vasudha,Tepe, Jetze J.
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p. 5091 - 5094
(2007/10/03)
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- Highly efficient dynamic kinetic resolution of azlactones by urea-based bifunctional organocatalysts
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Novel tasks for a venerable molecule: Bifunctional organocatalysts of the type shown, with a quasi Lewis acidic urea or thiourea unit and a Bronsted basic amine functionality, effect the dynamic kinetic resolution of azlactones with high enantioselectivit
- Berkessel, Albrecht,Cleemann, Felix,Mukherjee, Santanu,Mueller, Thomas N.,Lex, Johann
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p. 807 - 811
(2007/10/03)
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- Multicomponent synthesis of highly substituted imidazolines via a silicon mediated 1,3-dipolar cycloaddition
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A diastereoselective multicomponent synthesis of highly functionalized imidazolines is reported. A silicon mediated 1,3 dipolar cycloaddition of the in situ generated münchnone with an imine resulted in the formation of highly substituted imidazolines. The imidazolines contain a four-point diversity and two stereocenters and the cycloaddition reaction is applicable to aryl, alkyl, acyl, and heterocyclic substitutions.
- Peddibhotla,Tepe
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p. 1433 - 1440
(2007/10/03)
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- Flow-vacuum pyrolysis of 2,5-diphenyl-4-methyloxazole
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The flow-vacuum pyrolysis of 2,5-diphenyl-4-methyloxazole (4) at 1000°C and 0.5 Torr afforded a complex reaction mixture containing: benzonitrile, diphenylmethane, 9,10-dimethylphenantrene, 9,10-dimethylantracene, fluorene, o-benzylbenzonitrile (major product, 20-22%), phenanthrene, anthracene, o,o′-dicyanodiphenyl, 9,10-anthraquinone, 2-methyl-4,5-diphenyloxazole and 1,1,2,2-tetraphenylethane. A radical- and carbene mechanism is suggested in order to rationalize the formation of the reaction products.
- Banciu, Mircea D.,Istrati, Daniela,Schiketanz, Iosif,Mihǎiescu, Dan,Drǎghici, Constantin,Malacea, Raluca
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p. 493 - 499
(2007/10/03)
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- gem-diacetates as carbonyl surrogates for asymmetric synthesis. Total syntheses of sphingofungins E and F
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The equivalent of an asymmetric addition to a carbonyl group with a stabilized anion is accomplished by discriminating between the enantiotopic C-O single bonds of a gem-diacetate. In this way, enantioselective total syntheses of two antifugal agents, sph
- Trost,Lee
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p. 12191 - 12201
(2007/10/03)
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- Enantiomerically enriched alpha , alpha -distributed amino acids and method
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Compositions and methods for the preparation of enantiomerically enriched alpha , alpha -disubstituted amino acid precursors are presented. Briefly, allylic electrophiles are alkylated with oxazolones in the presence of a base and catalytic quantities of
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- Aminoketone, oxazole and thiazole synthesis. Part XIII. 1 new 2-aryl-6-phenyloxazoles with 4-methyl or 4-isopropyl groups
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Benzoylation of (±)-α-alanine and (±)-valine followed by cyclization afforded the corresponding azlactones, which reacted with benzene, toluene, o- and m-xylene yielding substituted N-benzoyl-phenacylamines. Their cyclization in the presence of phosphorus oxychloride led to the title compounds whose electronic and NMR spectra (1H and 13C) are presented.
- Schiketanz, Iosif,Istrati, Daniela,Drǎghici, Constantin,Balaban, Alexandru T.
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p. 137 - 142
(2007/10/03)
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- A kinetic study of the base-catalyzed dimerization of 5(4H)-oxazolones
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The effects of the substituent at position-2 and kind of the base on the rate of the base-catalyzed dimerization of 5(4H)-oxazolones have been investigated. The electrondonating and strong steric effect of the substituent at position-2 reduce markedly the proclivity of 5(4H)-oxazolones to dimerization. The following catalytic activity sequence of the bases has been found: DBU >> Et3N > (i-Pr)2EtN.
- Mazurkiewicz,Pierwocha,Fryczkowska
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p. 113 - 121
(2007/10/03)
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- Structures of b and a product ions from the fragmentation of argentinated peptides
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Argentinated (silver-containing) oligopeptides fragment under low- energy collision conditions to yield abundant argentinated product ions. The structures of the [b2 - H + Ag]+ and [a2 - H + Ag]+ ions have been determined by means of tandem mass spectrometry and confirmed by comparison with synthesized derivatives of the candidate [b2 - H + Ag]+ ion structure. The [b2 - H + Ag]+ ion was found to be an N-argentinated oxazolone, which could subsequently form the [a2 - H + Ag]+ ion and other product ions after collision activation. Tripeptides containing proline as their second residue were observed to form a relatively less abundant [b2 - H + Ag]+ ion, which was postulated to be an argentinated ketene.
- Lee, Vicky W.-M.,Li, Hongbo,Lau, Tai-Chu,Siu, K. W. Michael
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p. 7302 - 7309
(2007/10/03)
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- An efficient strategy to orthogonally protected (R)- and (S)-α-methyl(alkyl)serine-containing peptides via a novel azlactone/oxazoline interconversion reaction
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A novel strategy for the synthesis of (R)- and (S)-α-methyl(alkyl)serine-containing peptides is presented. Using (S)-phenylalanine cyclohexylamide 6 as chiral auxiliary, the optically pure azlactones (R)- and (S)-2 were synthesized via a novel azlactone/oxazoline interconversion reaction (Figures 3 and 6). These azlactones constitute fully protected and activated synthetic equivalents of (R)- and (S)-α-methylserine and can be directly incorporated into peptides without further protective group manipulations. Like other α,α-dialkylated glycines, optically pure α-alkylserines can be used to stabilize β-turn and α-helical conformations in short peptides.
- Obrecht, Daniel,Altorfer, Michael,Lehmann, Christian,Sch?nholzer, Peter,Müller, Klaus
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p. 4080 - 4086
(2007/10/03)
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- Studies on chromone derivatives : An efficient one-pot synthesis of various 3-( N-aroylamino)-3-methyl-4-(4-oxobenzopyran-3-yl)-1-( N,N-dimethylamino)azetidin-2-ones
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Chlorosulfonylmethylene(dimethyl)ammonium chloride 1 is found to be a highly reactive cyclodehydrating agent for the one-pot synthesis of various novel 3-(N-aroylamino)-3-methyl-4-(4-oxobenzopyran-3-yl)-1-(N,N-dimethylamino) azetidin-2-ones 5 from N-aroyl
- Boruah, Anima,Prajapati, Dipak,Sandhu, Jagir S.
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p. 1148 - 1151
(2007/10/03)
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- A reinvestigation of the α-alkylation of 4-monosubstituted 2-phenyloxazol-5(4H)-ones ('azlactones'): A general entry into highly functionalized α,α-disubstituted α-amino acids
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Novel, more reliable and general reaction conditions for the α-alkylation of 4-monosubstituted 2-phenyloxazol-5(4H)-ones (= 4-monosubstituted 2-phenyl-azlactones) rac-2 to 4,4-disubstituted 2-phenyloxazol-5(4H)-ones rac-1 were found. Thus, a whole range of highly functionalized rac-1 were prepared in medium-to-good overall yields (40-90%). Azlactones rac-1 are ideal precursors for the synthesis of optically pure α,α-disubstituted (R)- and (S)-α-amino acids.
- Obrecht,Bohdal,Ruffieux,Muller
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p. 1423 - 1429
(2007/10/02)
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